ProfG has been addressing the issue of brain shrinkage and asking-Which agents are the best?
We may not all agree on what is the best, but one can ask what is/are the worse.
If we can address this problem and agree, then surely it is time to say “It’s rubbish! Throw it in the Bin!” (A comment I once heard at an MS Life meeting)
The obvious answer is……yep you guessed it……
Lazy, risk-averse neurologists. who prescribe ineffective treatments
Surely we should do an Freedom of Information to find the Centres that prescribe alot of them and then one would know where to avoid:-0. These neuros are happy to prescribe treatments that are not going to do alot for most of their recipients, but they are easy to monitor.
Meanwhile tick, tock, tick, tock as your brain reserve is eaten…never to return.
Having looked at some pharma trials where their strong active drug was compared to these weak efficacy options we see people in the trials, permanently lose neurological function due to the two years on an ineffective (for the population) treatment, so pharma can get an easy positive result.
If doing trials in relapsing MS against placebo is considered unethical, Surely doing a trial against the “low-hanging fruit” is unethical too!!!
What do you think?…..The FDA (US regulators) and EMA (European regulators) surely don’t seem to care about your brain, as they seem to approve an endless stream of placebo-controlled trials
OK I sound like a stuck record and you are right and I don’t have the clinical qualifications.
Prof G is asking how do you assess brain volume loss. As this study shows you could go to a specialist imaging lab (which is why we see the same names on trial papers over and over again) or you can get a robot to measure it.
Beadnall HN, Wang C, Van Hecke W, Ribbens A, Billiet T, Barnett MH. Comparing longitudinal brain atrophy measurement techniques in a real-world multiple sclerosis clinical practice cohort: towards clinical integration? Ther Adv Neurol Disord. 2019 Jan 25;12:1756286418823462
Whole brain atrophy (WBA) estimates in multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. We compare Structural Image Evaluation using Normalisation of Atrophy (SIENA) with the icobrain longitudinal pipeline (icobrain long), for assessment of longitudinal WBA in MS patients.
Magnetic resonance imaging (MRI) scan pairs [1.05 (±0.15) year separation] from 102 MS patients were acquired on the same 3T scanner. Three-dimensional (3D) T1-weighted and two-dimensional (2D)/3D fluid-attenuated inversion-recovery sequences were analysed. Percentage brain volume change (PBVC) measurements were calculated using SIENA and icobrain long. Statistical correlation, agreement and consistency between methods was evaluated; MRI brain volumetric and clinical data were compared. The proportion of the cohort with ann ualized brain volume loss (aBVL) rates ⩾ 0.4%, ⩾0.8% and ⩾0.94% were calculated. No evidence of disease activity (NEDA) 3 (no relapses, no active MRI activity or clinical progression) and NEDA 4 (NEDA 3 +brain atrophy) were also determined.
Mean annualized PBVC was -0.59 (±0.65)% and -0.64 (±0.73)% as measured by icobrain long and SIENA. icobrain long and SIENA-measured annualized PBVC correlated strongly, r = 0.805 (p < 0.001), and the agreement and consistency were excellent. Weak correlations were found between MRI metrics and Expanded Disability Status Scale scores. Over half the cohort had aBVL ⩾ 0.4%, approximately a third ⩾0.8%, and aBVL was ⩾0.94% in 28.43% and 23.53% using SIENA and icobrain long, respectively. NEDA 3 was achieved in 35.29%, and NEDA 4 in 15.69% and 16.67% of the cohort, using SIENA and icobrain long to derive PBVC, respectively.
icobrain long quantified longitudinal WBA with a strong level of statistical agreement and consistency compared to SIENA in this real-world MS population. Utility of WBA measures in individuals remains challenging, but show promise as biomarkers of neurodegeneration in MS clinical practice. Optimization of MRI analysis algorithms/techniques are needed to allow reliable use in individuals. Increased levels of automation will enable more rapid clinical translation.
We have been discussing brain atrophy and this paper looks at brain volume loss in the real world using two different methods. Whilst they pat themselves on the back on how well the two measures correlate, it means that you have lost over 0.05% more brain if you use one method over the the other. If the average low of a healthy brain is 0.2%. thats a quarter more brain:-(
SIENA although a place in Italy is actually a method for estimating brain volume. It is widely used by expert MRI reading centres to measure the percentage WBV change (PBVC) between two time points in MS studies. The proposed pathological cut off of greater or equal to ⩾0.4% annualized BVL (as measured by SIENA) has been incorporated into the criteria for ‘no evidence of disease activity’ (NEDA) four .
Icobrain long apparently a more automated solution
Whilst this is not important in the context of this post, the point I want to make is let’s look at the real-life data. In the study they looked at people on treatment
Of the 73 patients on therapy at baseline; 40 were on the CRABS. At follow up we had 96 on treatment and 38 on CRABS and 4 on alemtumab and HSCT.
Now let’s look at the Brain atrophy paper. People on treatment are loosing 0.9% per year on treatment not that great if you consider profG was extolling the virtue of effective T cell inhibition reducing brain loss down to 0.2%, which is within the normal aging range.
So go on
This figure will be actually worse because half the sample had active treatments like natalizumab and fingolimod, meaning those would offset the worse treatments. Is is time to say Bye bye to CRABS